High-sensitivity single-shot perfusion-weighted fMRI.

A method is presented for measurement of perfusion changes during brain activation using a single-shot pulsed spin labeling technique. By employing a double-inversion labeling strategy, stationary tissue (background) signal was suppressed while minimally affecting perfusion sensitivity. This allowed omission of the otherwise required reference scan, resulting in twofold-improved temporal resolution. The method was applied to visual and motor cortex activation studies in humans, and compared to standard FAIR-type perfusion labeling techniques. Experiments performed at 1.5T and 3.0T indicate a close to 90% suppression of background signal, at a cost of an 11% and 9%, respectively, reduction in perfusion signal. Combined with the twofold increase in signal averaging, and a reduction in background signal fluctuations, this resulted in a 64% (1.5T, N = 3) and a 128% (3T, N = 4) overall improvement in sensitivity for the detection of activation-related perfusion changes. Magn Reson Med 46:88-94, 2001. Published 2001 Wiley-Liss, Inc.

Simultaneous BOLD/perfusion measurement using dual-echo FAIR and UNFAIR: sequence comparison at 1.5T and 3.0T.

Functional MRI (fMRI) studies designed for simultaneously measuring Blood Oxygenation Level Dependent (BOLD) and Cerebral Blood Flow (CBF) signal often employ the standard Flow Alternating Inversion Recovery (FAIR) technique. However, some sensitivity is lost in the BOLD data due to inherent T1 relaxation. We sought to minimize the preceding problem by employing a modified UN-inverted FAIR (UNFAIR) technique, which (in theory) should provide identical CBF signal as FAIR with minimal degradation of the BOLD signal. UNFAIR BOLD maps acquired from human subjects (n = 8) showed significantly higher mean z-score of approximately 17% (p < 0.001), and number of activated voxels at 1.5T. On the other hand, the corresponding FAIR perfusion maps were superior to the UNFAIR perfusion maps as reflected in a higher mean z-score of approximately 8% (p = 0.013), and number of activated voxels. The reduction in UNFAIR sensitivity for perfusion is attributed to increased motion sensitivity related to its higher background signal, and, T2 related losses from the use of an extra inversion pulse. Data acquired at 3.0T demonstrating similar trends are also presented.

Critical oxygen tension in rat brain: a combined (31)P-NMR and EPR oximetry study.

The relationship between cerebral interstitial oxygen tension (Pt(O(2))) and cellular energetics was investigated in mechanically ventilated, anesthetized rats during progressive acute hypoxia to determine whether there is a "critical" brain Pt(O(2)) for maintaining steady-state aerobic metabolism. Cerebral Pt(O(2)), measured by electron paramagnetic resonance oximetry, decreased proportionately to inspired oxygen fraction. (31)P-nuclear magnetic resonance measurements revealed no changes in P(i), phosphocreatine (PCr)/P(i) ratio, or intracellular pH when arterial blood oxygen tension (Pa(O(2))) was reduced from 145.1 +/- 11.7 to 56.5 +/- 4.4 mmHg (means +/- SE). Intracellular acidosis, a sharp rise in P(i), and a decline in the PCr/P(i) ratio developed when Pa(O(2)) was reduced further to 40.7 +/- 2.3 mmHg. The corresponding Pt(O(2)) values were 15.1 +/- 1.8, 8.8 +/- 0.4, and 6.8 +/- 0.3 mmHg. We conclude that over a range of decreasing oxygen tensions, cerebral oxidative metabolism is not sensitive to oxygen concentration. Oxygen becomes a regulatory substrate, however, when Pt(O(2)) is decreased to a critical level.

A protocol for assessing subtraction errors of arterial spin-tagging perfusion techniques in human brain.

A protocol for assessing signal contributions from static tissue (subtraction errors) in perfusion images acquired with arterial spin-labeling (ASL) techniques in human brain is proposed. The method exploits the reduction of blood T(1) caused by the clinically available paramagnetic contrast agent, gadopentetate dimeglumine (Gd-DTPA). The protocol is demonstrated clinically with multislice FAIR images acquired before, during, and after Gd-DTPA administration using a range of selective inversion widths. Perfusion images acquired postcontrast for selective inversion widths large enough (threshold) to avoid interaction with the imaging slice had signal intensities reduced to noise level, as opposed to subtraction errors manifested on images acquired using inversion widths below the threshold. The need for these experiments to be performed in vivo is further illustrated by comparison with phantom results. The protocol allows a one-time calibration of relevant ASL parameters (e.g., selective inversion widths) in vivo, which may otherwise cause subtraction errors. Magn Reson Med 43:896-900, 2000. Published 2000 Wiley-Liss, Inc.

Multislice perfusion imaging in human brain using the C-FOCI inversion pulse: comparison with hyperbolic secant.

Perfusion studies based on pulsed arterial spin labeling have primarily applied hyperbolic secant (HS) pulses for spin inversion. To optimize perfusion sensitivity, it is highly desirable to implement the HS pulse with the same slice width as the width of the imaging pulse. Unfortunately, this approach causes interactions between the slice profiles and manifests as residual signal from static tissue in the resultant perfusion image. This problem is currently overcome by increasing the selective HS width relative to the imaging slice width. However, this solution increases the time for the labeled blood to reach the imaging slice (transit time), causing loss of perfusion sensitivity as a result of T(1) relaxation effects. In this study, we demonstrate that the preceding problems can be largely overcome by use of the C-shaped frequency offset corrected inversion (FOCI) pulse [Ordidge et al., Magn Reson Med 1996;36:562]. The implementation of this pulse for multislice perfusion imaging on the cerebrum is presented, showing substantial improvement in slice definition in vivo compared with the HS pulse. The sharper FOCI profile is shown to reduce the physical gap (or "safety margin") between the inversion and imaging slabs, resulting in a significant increase in perfusion signal without residual contamination from static tissue. The mean +/- SE (n = 6) gray matter perfusion-weighted signal (DeltaM/M(o)) without the application of vascular signal suppression gradients were 1.19 +/- 0. 10% (HS-flow-sensitive alternating inversion recovery [FAIR]), and 1. 51 +/- 0.11% for the FOCI-FAIR sequence. The corresponding values with vascular signal suppression were 0.64 +/- 0.14%, and 0.91 +/- 0. 08% using the HS- and FOCI-FAIR sequences, respectively. Compared with the HS-based data, the FOCI-FAIR results correspond to an average increase in perfusion signal of up to between 26%-30%. Magn Reson Med 42:1098-1105, 1999.

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery.

Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model.

Rapid and continuous monitoring of cerebral perfusion by magnetic resonance line scan assessment with arterial spin tagging.

A new approach is presented for rapid and continuous monitoring of cerebral perfusion which is based upon line-scan MR column imaging with arterial spin tagging (AST) of endogenous water. Spin tagging of arterial water protons is accomplished using adiabatic fast passage inversion, followed by acquisition of the perfusion sensitive MR signal from a column placed at the desired level through the brain using line scan localization techniques. A perfusion sensitive line scan is followed by a non-perfusion sensitive line scan, and perfusion is calculated pixel-by-pixel from the intensity difference of the two lines. Continuous perfusion measurements are reported with temporal resolution of 10 s in pixels of volume 0.027 cm3 or less. Examples of the methodology are given during hypercapnic challenge induced with carbon dioxide, and during an ischemic event induced by reversible middle cerebral artery occlusion. The method is also used to characterize the signal response as a function of arterial inversion time and post inversion acquisition delay. These methods permit rapid and continuous monitoring of cerebral perfusion with high spatial resolution, and can be interleaved with MR measurements of diffusion and T1 to follow the progression of cerebral events during physiological or pharmacological intervention.

Perfusion imaging using FOCI RF pulses.

Pulsed arterial spin-tagging techniques for perfusion measurements (e.g., echo planar MR imaging and signal targeting with alternating radiofrequency (EPISTAR), flow-sensitive alternating inversion recovery (FAIR), quantitative imaging of perfusion using a single subtraction (QUIPPS), uninverted FAIR (UNFAIR)) generally use hyperbolic secant (HS) pulses for spin inversion. The performance of these techniques depends on the inversion efficiency, as well as the sharpness of the slice profiles. Frequency offset corrected inversion (FOCI) pulses, a recently proposed HS variant, can provide slice profiles with edges that can be up to 10 times sharper than those obtained with conventional HS pulses. In this communication, the implementation and application of the C-shape FOCI pulse for perfusion imaging in rat brain with the FAIR technique is summarized. Despite providing a more rectangular slice profile than a conventional HS pulse, it is demonstrated both theoretically and experimentally that the FAIR perfusion signal is not increased by using a FOCI tagging pulse. However, the use of a FOCI inversion pulse is shown to significantly minimize static signal subtraction errors that are common with conventional HS pulses. Finally, the suitability of the pulse for perfusion studies is demonstrated, in vivo, on rat brain.

The influence of preischemic hyperglycemia on acute changes in brain water ADCw following focal ischemia in rats.

The effect of preischemic hyperglycemia on the acute decline of brain apparent diffusion coefficient of water (ADCw) following cerebral ischemia was studied in a rat model of middle cerebral artery occlusion (MCAO). ADCw was measured by NMR with a newly developed spin-echo line-scan protocol that provides for an ADCw calculation every 15 s at a spatial resolution of 3.4 microl/pixel. A remote controlled occluding device was used to initiate ischemia from outside the magnet, allowing for continuous monitoring of ADCw before, during and after MCAO. Preischemic hyperglycemia (25-30 mM) was achieved via i.v. infusion of 50% glucose. The decline in ADCw following ischemia was analyzed to obtain three-time constants: the time from onset of ischemia to initial significant ADCw decline below baseline level (i.e., 20% of maximal decline, T0.20), the time to decline by 50% (T0.50), and the time to decline by 95% (T0.95). Mean (+/-S.D.) values for T0.20, T0.50, T0.95 were: 39.6+/-7.2, 54. 0+/-7.8, 105.0+/-15.0 s for the normoglycemic group (n=7), and 49. 2+/-33.0, 116.4+/-2.4, 351.0+/-189.0 s for the hyperglycemic group (n=6), respectively. Hyperglycemia significantly prolongs T0.50 and T0.95 but does not affect T0.20. The temporal profiles of ADCw decline following ischemia under normo- and hyperglycemia are distinctively different from the known time course of membrane depolarization under similar experimental conditions, suggesting that mechanisms other than membrane depolarization and cell swelling may contribute to changes in ADCw in cerebral ischemia.

The influence of preischemic hyperglycemia on acute changes in the apparent diffusion coefficient of brain water following global ischemia in rats.

We report the effect of increased plasma glucose levels on changes in the apparent diffusion coefficient of brain water (ADCw) during the first few minutes of global ischemia in rats. Brain ADCw values were acquired every 15 s using a diffusion-weighted line-scan MR pulse sequence. Preischemic hyperglycemia was achieved by infusion of 50% dextrose (i.v.) prior to KCl-induced cardiac arrest global ischemia. Analysis based on single voxels (3.4 microl) in brain demonstrated significant differences in the time course of ADCw decline between normoglycemic (n = 8) and hyperglycemic (n = 6) groups. Mean data from the hyperglycemic group indicated a biphasic decline of ADCw that was characterized by an initial rapid drop followed by a plateau of approximately 1 min before gradually declining and leveling off to its minimum value. In the normoglycemic group, ADCw declined to the same value as in the hyperglycemic group, but without a notable plateau. In the cerebral cortex, the times to maximal and half maximal ADCw drop following global ischemia in the hyperglycemic group were 3.96 and 2.26 min respectively. Corresponding time intervals for the normoglycemic group were 1.86 and 1.14 min, respectively. The time course for changes in ADCw demonstrated here is significantly different than that for anoxic depolarization reported under similar experimental conditions and suggests that events other than the complete loss of membrane ionic homeostasis and subsequent cell swelling may be involved in the initial decline of ADCw in global cerebral ischemia.

The application of diffusion-weighted line-scanning for the rapid assessment of water ADC changes in stroke at high magnetic fields.

Rapid changes in the apparent diffusion coefficient of water following brain ischemia have been extensively studied using echo planar diffusion imaging at low fields (2.0 T). There is a desire to perform these studies at higher fields (> 3.0 T) where the benefits of improved signal-to-noise can be exploited. Unfortunately, EPI diffusion is technically difficult to implement at high fields because of large magnetic susceptibility effects. This article demonstrates the feasibility of employing a line-scan diffusion protocol for ADCw measurements in stroke. The technique was applied on a 4.0 T system to monitor the decline in ADCw following the induction of focal cerebral ischemia in rat. ADCw data were acquired every 15 s with 10 b-values or every 22.5 s with 15 b-values, with a cubic spatial resolution of 1.5 mm. The results demonstrate that estimates of ADCw can be acquired with coefficients of variation under 3.0%, and with a combination of spatial and temporal resolution comparable to that previously reported for EPI.

Perfusion imaging by un-inverted flow-sensitive alternating inversion recovery (UNFAIR).

A new pulse sequence for estimating cerebral blood flow called UNFAIR, which uses a combination of sequential hyperbolic secant preparatory pulses, is introduced. This sequence is based on the same generalized conditions as previously introduced inversion recovery techniques except that the spins in the image slice of interest always have +z magnetization and the in-flowing spins are alternately inverted and uninverted. CBF-weighted images of rat brain under conditions of normocpnia and hypercapnia are presented and demonstrate the expected CBF response. A model describing the signal response to this pulse sequence is also presented and compared with in-vivo data acquired from gray and white matter.

A modified sub-second fast-STEAM sequence incorporating bipolar gradients for in vivo diffusion imaging.

A modified high-speed stimulated-echo acquisition mode (STEAM) diffusion sequence (90 degrees-TE/2-90 degrees-TM-[alpha-TE/2-STE]n) incorporating bipolar diffusion gradients that are less sensitive to macroscopic motion-induced artifacts is presented. Diffusion encoding was performed only during the first echo interval (TE1) with bipolar gradients that were implemented on all three mutually orthogonal axes. Calibration measurements on phantoms filled with water, isopropanol, and dimethyl sulfoxide yielded apparent diffusion coefficients (ADC) consistent with published values. Non-ECG-triggered in vivo images acquired on rat brain with relatively high b values (approximately 450 s/mm2) indicated minimal motion artifacts. Evaluated ADCs averaged over the cortex, left mid-brain, right mid-brain, regions yielded (0.91 +/- 0.02), (1.06 +/- 0.02), (1.01 +/- 0.03) x 10(-3) mm2s-1, respectively.

Fat suppression at 7T using a surface coil: application of an adiabatic half-passage chemical shift selective radiofrequency pulse.

The selective suppression of fat using chemical shift selective (CHESS) sinc, gaussian presaturation, or binomial radiofrequency pulses are widely implemented techniques in magnetic resonance imaging. For applications wherein transmitter coils that generate inhomogeneous magnetic (B1), fields are used (e.g., surface coils), adiabatic radiofrequency pulses that are less susceptible to spatial variations in B1 amplitude will improve the spatial homogeneity of spin excitation angle. Herein, we describe the application of an adiabatic half-passage hyperbolic secant CHESS pulse suitable for acquiring fat-suppressed magnetic resonance images with surface coils on high-field systems. Images obtained from a water/fat phantom and from the abdominal region of a rat are presented indicating excellent suppression of fat signal from the entire coil-sensitive volume.

High resolution renal diffusion imaging using a modified steady-state free precession sequence.

A modified steady-state free precession (SSFP) diffusion sequence is proposed for high resolution renal imaging. A pair of bipolar diffusion gradients was used to minimize the errors in measured apparent diffusion coefficient (ADC) caused by variations in T1, T2, and RF flip angle that have been observed with previously employed SSFP diffusion sequences. Motion sensitivity was reduced by the use of compensated gradients, frame-by-frame averaging, and a repetition time of 22 ms, which for a single-acquisition 128 x 128 image requires only 3 s. High resolution was achieved by signal averaging. The modified sequence was applied to in vivo diffusion measurements. In six normal rat kidneys the ADCs (mean +/- SD; x 10(-3) mm2/s) of the cortex, outer medulla, and inner medulla were 2.28 +/- 0.05, 2.38 +/- 0.10, and 2.95 +/- 0.05, respectively. The technique requires relatively large gradients to achieve adequate diffusion weighting.